Microscopic (electron microscopy-including tracers, freeze-cleavage replication techniques and antibody labeling methods; enzyme cytochemistry at light and electron microscopy levels), biochemical, and molecular biology approaches will be used: (a) to study the structure of cytoplasmic organelles in order to gain a better understanding of organelle functions in normal, pathologic and malignant cells; and (b) to search for differences between malignant and normal cells in basic mechanisms of organelle-organelle and cell-cell interrelations. Dynamic interrelations of endoplasmic reticulum (including GERL) to the plasma membrane, Golgi apparatus, lysosomes and microperoxisomes will be studied in altered hepatocytes (in rats or hamsters: fed hypolipidemic drugs; partially-hepatectomized; or treated with N-2-fluorenylacetamide (FAA) to produce hepatic nodules). Also FAA-induced rat hepatomas, those that produce normal plasma proteins and alpha-1-fetoprotein and those that do not; the rapidly-growing Novikoff hepatoma of rats; and a transplantable amelanotic melanoma of hamsters (Greene). Isolation by density equilibration centrifugation will be attempted of: (a) the lipid-containing lysosomes (lipolysosomes) of hamster hepatocytes; and (b) elements of the greatly enlarged Golgi apparatus of hamster hepatocytes following partial hepatectomy. Lipoprotein apoproteins will be studied in the FAA-produced hepatomas, and in rat hepatocytes in which the synthetic or degradative pathways are stimulated. The synthesis and assembly of cell surface glycoproteins, including specific molecular species, will be studied in cultured cells, normal and malignant. The sites of syntheses of nucleic acid, protein and membrane components of oncogenic viruses will also be studied. This will involve newly-evolved techniques of studying sugar moieties, as well as autoradiography and immunocytochemistry. BIBLIOGRAPHIC REFERENCES: Cytochemical studies on Golgi apparatus, GERL and lysosomes in neurons of dorsal root ganglia in mice. Boutry, J.-M., and Novikoff, A.B. Proc. Nat. Acad. Sci USA 72:508-512,1975. Cytochemical studies on rat hepatocytes following Nafenopin treatment. Novikoff, A.B. Novikoff, P.M., Mori, M., and Levine, W. J. Histochem. Cytochem., 23:314-315, 1975.